Abstract 4782: Inducing abscopal effect in colorectal cancer via antibody-conjugated photothermal nanoparticles in combination with immunocytokine

Abstract Colorectal cancer is characterized by high rates of recurrence and metastasis, making it particularly challenging to manage due to multidrug resistance after treatment and/or the difficulty of detecting metastatic lesions. Photothermal therapy (PTT) has emerged as a promising strategy to overcome the drug resistance, with ongoing studies investigating its potential to induce the abscopal effect—an immune-mediated response targeting metastatic cancer. However, current research indicates that PTT alone is insufficient to trigger a significant abscopal effect and requires combination with immune modulators, such as immune checkpoint inhibitors or immune stimulating cytokines. Interferon-β (IFN-β), a cytokine capable of directly inducing tumor cell death, also exhibits anticancer effects through immune cell modulation. We hypothesized that combining PTT with IFN-β could induce a synergistic response, enhancing the abscopal effect. In a previous study, we developed antibody-conjugated polydopamine (PDA) nanoparticles targeting Claudin-3 (CLDN3), a protein overexpressed in various cancers, including colorectal cancer, to serve as a material for PTT. In addition, we utilized a CLDN3-targeting antibody-IFN-β mutein fusion protein (ABN202, αCLDN3) to enhance the abscopal effect. The objective of this study was to evaluate whether combining PTT with ABN202 (αCLDN3-IFN-β) could synergistically enhance immune cell activation compared to each treatment alone. Moreover, in human interferon receptor 1/2 knock-in mice, the combination effectively inhibited tumor growth at distant sites. It also demonstrated that the efficacy in preventing recurrence when tumor was re-challenged after the treatment. Therefore, these findings suggest that PTT in combined with ABN202 (αCLDN3-IFN-β) is a promising a novel therapeutic strategy for preventing cancer metastasis and recurrence in colorectal cancer. Citation Format: Myeung Ryun Seo, Jinwon Park, Hee Geon Park, Jae Choi, Sang Moo Lee, Sangin Lee, Sae Hyung Lee, Hobin Yang, Sungyoul Hong, Yu-Kyoung Oh, Young Kee Shin. Inducing abscopal effect in colorectal cancer via antibody-conjugated photothermal nanoparticles in combination with immunocytokine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4782.